Goto, T. et al. have reported a monoclonal antibody (mouse anti-HM1.24 antibody) that was obtained by immunizing human plasma cells and that specifically recognizes an antigen with a molecular weight of 29-33 kDa specifically expressed in B cell lines (Blood (1994) 84, 1922-1930). The antigen recognized by mouse anti-HM1.24 antibody is referred to as HM1.24 antigen. When anti-HM1.24 antibody was administered to a mouse transplanted with human myeloma cells, the antibody accumulated in tumor tissues in a specific manner (Masaaki Kosaka et al., Nippon Rinsho (Japan Clinical) (1995) 53, 627-635), suggesting that anti-HM1.24 antibody could be applied in the diagnosis of tumor localization by radioisotopic labeling, missile therapies such as radiotherapy, and the like.
In the above Blood (1994) 84, 1922-1930, it has been described that anti-HM1.24 antibody has an in vitro cytotoxic activity on a human myeloma cell line RPMI8226. There have also been prepared a chimeric anti-HM1.24 antibody in which the constant region of a mouse anti-HM1.24 antibody has been replaced with a human constant region and a humanized anti-HM1.24 antibody (reshaped anti-HM1.24 antibody) in which the complementarity determining region (CDR) of a mouse anti-HM1.24 antibody has been grafted to a human antibody and some FR amino acids have been replaced (WO 98/14580). It has also been shown that chimeric anti-HM1.24 antibody and a humanized anti-HM1.24 antibody specifically bind to myeloma cells and have a cytotoxic activity (Blood (1999) 93, 3922-3930).
On the other hand, it has also been demonstrated for lymphatic tumors that an antigen protein (HM1.24 antigen) recognized by anti-HM1.24 antibody is expressed in lymphatic tumors and that anti-HM1.24 antibody has a cytotoxic activity on lymphatic tumors due to a complement-dependent cytotoxicity (CDC activity) and an antibody-dependent cellular cytotoxicity (ADCC activity), and thereby exhibits anti-tumor effect (WO 98/35698).
Thus, HM1.24 antigen has been highly expressed in a specific manner not only on myeloma cells that are terminally differentiated B cells but also in lymphatic tumors, and the anti-HM1.24 antibody, in particular humanized anti-HM1.24 antibody, that recognizes HM1.24 antigen, is useful as a therapeutic agent for myeloma including multiple myeloma and lymphatic tumors.
As anti-HM1.24 antibody binds to HM1.24 antigen expressed on the surface of target cells and exhibits cell-killing activity through the CDC activity and the ADCC activity, said activities depend on the amount of HM1.24 antigen expressed on the surface of target cells. Thus, if the amount of HM1.24 antigen expressed on tumor cells of subject patients could be determined when predicting the effect of anti-HM1.24 antibody, in particular humanized anti-HM1.24 antibody, on patients with multiple myeloma or patients with lymphatic tumors, precise prediction of therapeutic effects would become possible.